RT info:eu-repo/semantics/article
T1 Solubilization and stabilization of sodium dicloxacillin by cyclodextrin inclusion
A1 Echezarreta López, María Magdalena
A1 Otero-Mazoy, Iria
A1 Ramírez, Héctor Luís
A1 Villalonga, Reynaldo
A1 Torres-Labandeira, Juan José
A2 Ingeniería Química y Tecnología Farmacéutica
K1 Benzylpenicillin
K1 cyclodextrin
K1 solubility
K1 drug stability
K1 molecular modeling
AB The aim of this work is to analyze the effect of cyclodextrin (CD) complexation on the solubilization and stabilization of sodium dicloxacillin in acid aqueous solutions. The effect of four cyclodextrins -, -, - and hydroxypropyl--CD was studied. Phase solubility diagrams obtained are AL or BS type, depending on the cyclodextrin used and on the pH of the solution. The highest stability constants of the inclusion complexes are obtained with -CD at pH 1 and 2 and HP-CD at pH 3. The structure of the inclusion complex in solution is characterized by nuclear magnetic resonance (1H-NMR). This study suggests that the 7-oxo-4-thia-1-azabicyclo group is located in the CD cavity. Nevertheless, molecular modelling calculations predict two different orientations of dicloxacillin in the -CD cavity in vacuum and in aqueous solution. In vacuum, the results predict the inclusion of the dichlorophenyl ring of dicloxacillin instead of 7-oxo-4-thia-1-azabicyclo group into the -CD cavity. However, the results are different in aqueous solution and this conformation is confirmed by the NMR study. The effect of -CD and HP-CD in the stability of the drug in solution was studied. The degradation of sodium dicloxacillin in solution follows a pseudo-first-order kinetics and the cyclodextrin do not change this fact. Both cyclodextrins increase the stability of the drug but the efficacy is higher with -CD
YR 2008
FD 2008
LK http://riull.ull.es/xmlui/handle/915/37318
UL http://riull.ull.es/xmlui/handle/915/37318
LA en
NO Financiado por Xunta de Galicia (PGIDT07CSA002203PR) y Ministerio de Educación y Ciencia, FEDER (SAF 2005-01930.)
DS Repositorio institucional de la Universidad de La Laguna
RD 23-dic-2024